Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 33-year-old woman without evidence of previous liver disease developed fulminant hepatic failure following the therapeutic dose of acetaminophen 3 days prior to admission. At admission, liver and renal function revealed hepatocellular injury with jaundice, and acute renal failure, total serum bilirubin 12.5 mg/ dL, direct serum bilirubin 8.1 mg/dL, aspartate aminotransferase 8460 IU/L, alanine aminotransferase 4640 IU/L, blood urea nitrogen 36 mg/dL, and serum creatinine 5.2 mg/dL. Two days later she developed multiorgan failure including hemodynamic disturbance with irreversible shock, and expired. Autopsy was performed, liver pathology showed severe centrilobular and midzonal necrosis, compatible with toxic hepatic necrosis, and renal pathology showed focal loss of tubular epithelial cells and partial occlusion of tubular lumen by cellular debris, compatible with acute tubular necrosis. Physicians should be aware of potential hepatotoxicity and nephrotoxicity of acetaminophen, even if given at therapeutic dosage in acute febrile illness.
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PMID:Therapeutic dose of acetaminophen with fatal hepatic necrosis and acute renal failure. 1762 27

We report two children with hemolytic anemia during the course of hepatitis A infection. On admission, the patients had high blood urea nitrogen, creatinine, and uric acid levels, as well as anemia, leucocytosis, and direct and indirect hyperbilirubinemia. Both patients had a glucose-6-phosphate dehydrogenase deficiency (G6PD) and autoimmune antibodies. They were given vitamin K on admission. Inadvertent administration of vitamin K could have been related to an acute reduction in hemoglobin concentration. To prevent renal damage, plasmapheresis with fresh frozen plasma was done to clear bilirubin and plasma hemoglobin. The hyperbilirubinemia responded to plasmapheresis. However, acute tubular necrosis complicated the clinical course in one patient, and several sessions of hemodialysis were required. In conclusion, intravascular hemolysis should be considered in patients with hepatitis A infection, marked hyperbilirubinemia, and anemia. Although hepatitis A vaccination is not yet recommended for routine administration, high-risk patients, including those with a G6PD deficiency, should be vaccinated against hepatitis A.
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PMID:Etiology of hemolysis in two patients with hepatitis A infection: glucose-6-phosphate dehydrogenase deficiency or autoimmune hemolytic anemia. 1832 Feb 20

Activated neutrophils have been implicated in the development of ischemia/reperfusion (I/R)-induced renal failure. Cytokine-induced neutrophil chemoattractant-1 (CINC-1), a major factor in acute inflammation, is responsible for the activation of neutrophils and for neutrophil chemotaxis to sites of injury. Atrial natriuretic peptide (ANP), a hormone synthesized by the cardiac atria, was shown to possess anti-inflammatory potential due to its potency to inhibit the production of inflammatory mediators. We examined whether the human form of ANP attenuates I/R-induced renal injury by reducing neutrophil activation in a rat model. Male Wistar rats weighing 200-240 g were observed for 24 h after reperfusion following 45-min renal ischemia. Rats were intravenously administered alpha-human ANP (alpha-hANP, 0.2 microg/kg/min) beginning immediately after ischemia and continuing for 2 h after reperfusion. CINC-1 and myeloperoxidase (MPO) concentrations were measured to assess activation of the infiltrating neutrophil. Blood urea nitrogen and serum creatinine and urinary N-acetyl beta-d-glucosaminidase (NAG) were measured as indicators of glomerular function and as a specific indicator of proximal tubular function, respectively. alpha-hANP significantly inhibited I/R-induced increases in renal CINC-1 and MPO concentrations. alpha-hANP also reduced I/R-induced increases in the concentrations of blood urea nitrogen and serum creatinine, and improved histopathologic changes, including acute tubular necrosis. These findings indicate that alpha-hANP attenuates I/R-induced acute renal injury, at least in part by reducing neutrophil activation, and may be useful in surgeries, associated with renal ischemia, as well as in renal transplantation.
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PMID:Atrial natriuretic peptide attenuates ischemia/reperfusion-induced renal injury by reducing neutrophil activation in rats. 1864 86

Renal ischemia/reperfusion (I/R) injury is one of the main causes of postoperative renal failure. Activated neutrophils are implicated in the development of I/R-induced renal failure. JTE-607 has been reported to be a potent inhibitor of the multiple inflammatory cytokines in the endotoxic shock mouse model and heart Langendorff perfusion model. In this study, we examined whether JTE-607 attenuates I/R-induced renal injury by reducing neutrophil activation. Male wistar rats were intravenously administered JTE-607 (JTE group, 30 mg/kg) or 5% mannitol (control group) 30 min before ischemia. JTE-607 reduced the I/R-induced increases in the serum concentrations of blood urea nitrogen and creatinine, and improved the histopathologic changes, including acute tubular necrosis. I/R-induced an increase in neutrophil activation, reflected by increases in renal cytokine-induced neutrophil chemoattractant (CINC)-1 and myeloperoxidase (MPO) concentrations which were significantly reduced by JTE-607. These findings indicate that JTE-607 attenuates I/R-induced acute renal injury, probably by inhibiting neutrophil activation. JTE-607 might be a novel therapeutic strategy for the protection of postoperative renal failure in surgery associated with renal ischemia as well as renal transplantation.
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PMID:JTE-607, an inflammatory cytokine synthesis inhibitor, attenuates ischemia/reperfusion-induced renal injury by reducing neutrophil activation in rats. 1869 26

IL-18 function is neutralized in IL-18 binding protein transgenic (IL-18BP Tg) mice. First, we determined whether IL-18BP Tg mice are protected against ischemic acute kidney injury (AKI). Ischemic AKI was induced by bilateral renal pedicle clamping. IL-18BP Tg mice were functionally and histologically protected against ischemic AKI as determined by blood urea nitrogen, serum creatinine, and acute tubular necrosis score. We have demonstrated that the injurious effect of IL-18 in the kidney is independent of neutrophils and lymphocytes. Thus the effect of IL-18 inhibition on renal macrophage infiltration was determined. The number of macrophages was significantly reduced in IL-18BP Tg compared with wild-type kidneys. To determine the cytokines and chemokines that are dependent on IL-18, we performed flow cytometry based assays. Multiple chemokines/cytokines, IL-3, IL-6, IL-15, IL-18, leukemia inhibitory factor, macrophage colony-stimulating factor, macrophage inflammatory protein-2, granulocyte-macrophage colony-stimulating factor, and monocyte chemotactic protein-1 were significantly increased in AKI vs. sham kidneys. Only CXCL1 (also known as KC or IL-8) was significantly increased in AKI vs. sham kidneys and significantly reduced in IL-18BP Tg AKI vs. wild-type AKI kidneys. To determine whether macrophages are the source of CXCL1 in the kidney, we depleted macrophages with liposomal encapsulated clodronate. CXCL1 was significantly decreased in macrophage-depleted vs. control AKI mice. In summary, in ischemic AKI in mice, 1) IL-18BP Tg mice are functionally and histologically protected, 2) macrophage infiltration in the kidney and CXCL1 are significantly reduced in IL-18BP Tg mice, and 3) macrophage depletion significantly reduces CXCL1 in the kidney. In conclusion, protection against ischemic AKI in IL-18BP Tg mice is associated with less macrophage infiltration and less production of CXCL1 in the kidney.
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PMID:Interleukin-18 binding protein transgenic mice are protected against ischemic acute kidney injury. 1875 96

Ischemia/reperfusion (I/R) injury in organ transplantation significantly contributes to graft failure and is untreatable using current approaches. I/R injury is associated with activation of the complement system, leading to the release of anaphylatoxins, such as C5a, and the formation of the membrane attack complex. Here, we report a novel therapy for kidney I/R injury through silencing of the C5a receptor (C5aR) gene using siRNA. Mice were injected with 50 microg of C5aR siRNA 2 days before induction of ischemia. Renal ischemia was then induced through clamping of the renal vein and artery of the left kidney for 25 minutes. The therapeutic effects of siRNA on I/R were evaluated by assessment of renal function, histopathology, and inflammatory cytokines. siRNA targeting C5aR efficiently inhibited C5aR gene expression both in vitro and in vivo. Administering C5aR siRNA to mice preserved renal function from I/R injury, as evidenced by reduced levels of serum creatinine and blood urea nitrogen in the treated groups. Inhibition of C5aR also diminished in vivo production of the pro-inflammatory cytokine tumor necrosis factor-alpha and chemokines MIP-2 and KC, resulting in the reduction of neutrophils influx and cell necrosis in renal tissues. This study demonstrates that siRNA administration represents a novel approach to preventing renal I/R injury and may be used in a variety of clinical settings, including transplantation and acute tubular necrosis.
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PMID:Gene silencing of complement C5a receptor using siRNA for preventing ischemia/reperfusion injury. 1877 41

Malaria is an infectious disease caused by plasmodium, which lives and breeds in human blood cells, and is transmitted through the bites of Anopheles mosquitoes. Renal impairment, often caused by malaria, is acute renal failure (ARF) due to acute tubular necrosis (ATN). Dengue virus is transmitted from human to human through Aedes aegypti mosquito bites. Dengue hemorrhagic fever (DHF), the most severe stage of infection, is characterized by bleeding and shock tendencies (dengue shock syndrome, DSS). ARF is a less common complication in patients with DHF, with an incidence of less than 10%. Mixed infections of two infectious agents may cause overlapping symptoms and have been reported in Africa and India. We report here a patient with ARF due to mixed infection of severe malaria and DSS. The patient presented with fever and had a history of repeated malaria infection. Physical examination revealed stable vital signs and hepatosplenomegaly. Laboratory data showed hemoconcentration, thrombocytopenia and increased serum aminotransferase. Chest X-ray showed pleural effusion. A malarial antigen and thick smear examination showed the trophozoite stage of P. falciparum. On Day 3, blood pressure dropped to 80/60 mmHg, pulse was 120 beats/minute, weak, and body temperature 36.8 C, with icterus. Other tests revealed an increase of serum urea nitrogen and creatinine levels, and serologically anti-dengue IgG antibody (+) and anti-dengue IgM antibody (-). Based on these findings, we diagnosed the patient as having both malaria and DDS. We treated the patient with the parenteral anti-malarial agent, artemisinin. Supportive treatment and treatment of complications were also performed simultaneously for DSS. The patient experienced an oliguria episode but responded well to a diuretic. The patient was discharged after clinical and laboratory examinations showed positive progress.
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PMID:Acute renal failure in a patient with severe malaria and dengue shock syndrome. 1900 May 45

Acute renal failure (ARF) is mainly characterized by acute tubular necrosis. No significant change was found for mortality rates over the past few decades despite significant advances in supportive care. In recent years, great effort has been focused on traditional and herbal medicine, which is much less toxic than those agents conventionally used and which is nowadays considered as a novel therapeutic agent for ARF. However, the effect of ginsenosides (GS) administered orally on ARF has not been reported yet and little is known about its cellular and molecular mechanism. The purpose of the study is to investigate the protective effect of ginsenoside in rats with ARF on the changes of tyrosine hydroxylase immunoreactivity (TH-IR) as well as on the involvement of mitogen-activated protein kinases (MAPK) in the locus coeruleus. In our assay, glycerol-induced acute renal failure in rats was employed to study the protective effects of ginsenoside. Our results indicated that the treatment of ARF rats with ginsenosides for 48 h significantly reduced the serum blood urea nitrogen, creatinine level, and lipid peroxidation, restored the GSH level and the normal renal morphology. Immunohistochemistry showed that an obvious increase of TH-IR was further enhanced in ARF+GS group. The same effect was also observed in the changes of p-ERK1/2-IR in the locus coeruleus. Our results suggest that ginsenoside administered orally may have a strong renal protective effect against glycerol-induced ARF, and ginsenoside can also activate the brain catecholaminergic neurons in the locus coeruleus. Our future attention will be focused to the question whether there is a correlation between the renal protective effect of ginsenosides against acute renal failure and the activation of tyrosine hydroxylase in the locus coeruleus.
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PMID:Protective effect of ginsenoside against acute renal failure and expression of tyrosine hydroxylase in the locus coeruleus. 1924 9

Recent studies have shown the remarkable gender differences in the susceptibility or expression of many diseases. The mechanism underlying the gender differences is unclear. In the present study, we evaluated the effects of gender differences and different ischemia time on the renal ischemia-reperfusion injury (IRI). The IRI was induced in the bilateral kidneys of 156 male and 30 female BALB/c mice. Renal function, serum creatinine and blood urea nitrogen, and pathology of the kidneys were examined at 24 hr after IRI. Renal IRI was generated successfully in 182 of 186 mice with a 97.85% success rate. The levels of serum creatinine and blood urea nitrogen were significantly increased in male mice subjected to 30 min, 35 min, or 45 min of renal ischemia and in female mice subjected to 75 min of renal ischemia, compared to the control group at 24 hr after operation. In males following 35 min or 45 min of ischemia and in females following 75 min of ischemia, typical acute tubular necrosis was found in the areas of corticomedullary junction and the histopathologic scores, which represent the degree of renal tissue injuries, were significantly increased. In view of our data, the kidneys of male are much more susceptible to IRI than those of female. The optimal ischemia time of kidney is 35-45 min in males and 75 min in females for generating a stable model of IRI in mice. Investigation of the gender differences might provide a new area for mechanistic study of renal IRI.
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PMID:Gender differences in the susceptibility to renal ischemia-reperfusion injury in BALB/c mice. 1963 37

Hyperglycemia amplifies the inflammatory state after ischemia/reperfusion (I/R), and activated neutrophils have been implicated in the development of I/R-induced renal injuries. D-ribose is a naturally occurring monosaccharide found in all living cells. In this study, we examined whether D-ribose attenuates I/R-induced renal injury by reducing neutrophil activation in rats with transient hyperglycemia. Male Wistar rats were divided into sham (n = 24), control (n = 64), and D-ribose (n = 32) groups. Rats received intraperitoneal injection of glucose (3 g/kg) 30 min before induction of ischemia to induce transient hyperglycemia. Anesthetized rats underwent right nephrectomy and subsequent occlusion of the left renal artery and vein for 45 min. D-ribose (400 mg/kg) was intravenously administered 30 min before induction of ischemia. D-ribose significantly reduced the degree of the I/R-induced increases in renal concentrations of cytokine-induced neutrophil chemoattractant-1 (a chemotactic factor for the activation of neutrophils and chemotaxis to the site of injury) and myeloperoxidase (an indicator of neutrophils infiltration). D-ribose also reduced the I/R-induced increases in serum levels of blood urea nitrogen and creatinine, and improved histological changes, including acute tubular necrosis in the corticomedullary junction fields. These results indicate that D-ribose reduces the I/R-induced acute renal injury in rats with transient hyperglycemia, probably by reducing neutrophil activation. D-ribose might thus be useful for surgical procedures, such as renal transplant surgery, under hyperglycemia.
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PMID:Protective action of D-ribose against renal injury caused by ischemia and reperfusion in rats with transient hyperglycemia. 1985 Oct 50


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